Theoretical Considerations of the Prigogine–Defay Ratio with Regard to the Glass-Forming Ability of Drugs from Undercooled Melts

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Autor:innen
Wyttenbach, Nicole
Alsenz, Jochem
Autor:in (Körperschaft)
Publikationsdatum
2016
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Molecular Pharmaceutics
Themenheft
Link
Reihe / Serie
Jahrgang / Band
13
Ausgabe / Nummer
1
Seiten / Dauer
241–250
Patentnummer
Verlag / Herausgebende Institution
American Chemical Society
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Drug behavior in undercooled melts is highly important for pharmaceutics with regard to amorphous solid dispersions, and therefore, categories were recently introduced that differentiate glass formers (GFs) from other drugs that are nonglass formers (nGFs). The present study is based on the assumption that molecular properties relevant for the so-called Prigogine-Defay (PD) ratio would be indicative of a drug's glass-forming ability. The PD ratio depends in theory on the entropy of fusion and molar volume. Experimental data were gathered from a broad set of pharmaceutical compounds (n = 54) using differential scanning calorimetry. The obtained entropy of fusion and molar volume were indeed found to significantly discriminate GFs from nGFs. In a next step, the entropy of fusion was predicted by different in silico methods. A first group contribution method provided rather unreliable estimates for the entropy of fusion, while an alternative in silico approach seemed more promising for drug categorization. Thus, a significant discrimination model employed molar volume, a so-called effective hydrogen bond number, and effective number of torsional bonds (or torsional units) to categorize GFs and nGFs (p ≤ 0.0000). The results led to new insights into drug vitrification and to practical rules of thumb. The latter may serve as guidance in pharmaceutical profiling and early formulation development with respect to amorphous drug formulations.
Schlagwörter
amorphous drug, crystallization tendency, glass-forming ability, in silico prediction, undercooled melt
Fachgebiet (DDC)
Projekt
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1543-8384
1543-8392
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
WYTTENBACH, Nicole, Wiebke KIRCHMEYER, Jochem ALSENZ und Martin KUENTZ, 2016. Theoretical Considerations of the Prigogine–Defay Ratio with Regard to the Glass-Forming Ability of Drugs from Undercooled Melts. Molecular Pharmaceutics. 2016. Bd. 13, Nr. 1, S. 241–250. DOI 10.1021/acs.molpharmaceut.5b00688. Verfügbar unter: http://hdl.handle.net/11654/23709